Magnetic resonance (MR) imaging after ultra-small super paramagnetic iron oxide (USPIO) injection and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperative axillary lymph node staging in patients with breast cancer were evaluated using histopathologic findings as the reference standard. USPIO-enhanced MR and FDG-PET were performed in ten patients with breast cancer who were scheduled for surgery and axillary node resection. T2-weighted fast spin echo, T1-weighted three-dimensional (3D) gradient echo, T2*-weighted gradient echo and gadolinium-enhanced T1-weighted 3D gradient echo with spectral fat saturation were evaluated. MR imaging before USPIO infusion was not performed. The results were correlated with FDG-PET (acquired with dedicated PET camera, visual analysis) and histological findings. The histopathologic axillary staging was negative for nodal malignancy in five patients and positive in the remaining five patients. There was one false positive finding for USPIO-enhanced MR and one false negative finding for FDG-PET. A sensitivity (true positive rate) of 100%, specificity (true negative rate) of 80%, positive predictive value of 80%, and negative predictive value of 100% were achieved for USPIO-enhanced MR and of 80%, 100%, 100%, 80% for FDG-PET, respectively. The most useful sequences in the detection of invaded lymph nodes were in the decreasing order: gadolinium-enhanced T1-weighted 3D gradient echo with fat saturation, T2*-weighted 2D gradient echo, T1-weighted 3D gradient echo and T2-weighted 2D spin echo. In our study, USPIO-enhanced T1 gradient echo after gadolinium injection and fat saturation emerged as a very useful sequence in the staging of lymph nodes. The combination of USPIO-enhanced MR and FDG-PET achieved 100% sensitivity, specificity, PPV and NPV. If these results are confirmed, the combination of USPIO MR with FDG-PET has the potential to identify the patient candidates for axillary dissection versus sentinel node lymphadenectomy.